Category: Laboratory investigation

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Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects

Acute human brain responses to intracortical microelectrode arrays- challenges and future prospects

Front.Neuroeng. 7:24, 1-6

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons.

As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns).

However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies.

Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

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Computational Fluid Dynamic Analysis of Intracranial Aneurysmal Bleb Formation

Computational Fluid Dynamic Analysis of Intracranial Aneurysmal Bleb Formation

Neurosurgery 73:1061–1069, 2013

The management of unruptured aneurysms is controversial, with the decision to treat influenced by aneurysm characteristics including size and morphology. Aneurysmal bleb formation is thought to be associated with an increased risk of rupture.

OBJECTIVE: To correlate computational fluid dynamic (CFD) indices with bleb formation.

METHODS: Anatomic models were constructed from 3-dimensional rotational angiography data in 27 patients with cerebral aneurysms harboring a single bleb. Additional models representing the aneurysm before bleb formation were constructed by digitally removing the bleb. We characterized hemodynamic features of models both with and without the blebs using CFDs. Flow structure, wall shear stress (WSS), pressure, and oscillatory shear index (OSI) were analyzed.

RESULTS: There was a statistically significant association between bleb location at or adjacent to the point of maximal WSS (74%, P = .019), irrespective of rupture status. Aneurysmal blebs were related to the inflow or outflow jet in 89% of cases (P < .001), whereas 11% were unrelated. Maximal wall pressure and OSI were not significantly related to bleb location. The bleb region attained a lower WSS after its formation in 96% of cases (P < .001) and was also lower than the average aneurysm WSS in 86% of cases (P < .001).

CONCLUSION: Cerebral aneurysm blebs generally form at or adjacent to the point of maximal WSS and are aligned with major flow structures. Wall pressure and OSI do not contribute to determining bleb location. The measurement of WSS using CFD models may potentially predict bleb formation and thus improve the assessment of rupture risk in unruptured aneurysms.

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Foramen ovale puncture, lesioning accuracy, and avoiding complications

FO puncture

J Neurosurg 119:1176–1193, 2013

Foramen ovale (FO) puncture allows for trigeminal neuralgia treatment, FO electrode placement, and selected biopsy studies. The goals of this study were to demonstrate the anatomical basis of complications related to FO puncture, and provide anatomical landmarks for improvement of safety, selective lesioning of the trigeminal nerve (TN), and optimal placement of electrodes.

Methods. Both sides of 50 dry skulls were studied to obtain the distances from the FO to relevant cranial base references. A total of 36 sides from 18 formalin-fixed specimens were dissected for Meckel cave and TN measurements. The best radiographic projection for FO visualization was assessed in 40 skulls, and the optimal trajectory angles, insertion depths, and topographies of the lesions were evaluated in 17 specimens. In addition, the differences in postoperative pain relief after the radiofrequency procedure among different branches of the TN were statistically assessed in 49 patients to determine if there was any TN branch less efficiently targeted.

Results. Most severe complications during FO puncture are related to incorrect needle placement intracranially or extracranially. The needle should be inserted 25 mm lateral to the oral commissure, forming an approximately 45° angle with the hard palate in the lateral radiographic view, directed 20° medially in the anteroposterior view. Once the needle reaches the FO, it can be advanced by 20 mm, on average, up to the petrous ridge. If the needle/radiofrequency electrode tip remains more than 18 mm away from the midline, injury to the cavernous carotid artery is minimized. Anatomically there is less potential for complications when the needle/radiofrequency electrode is advanced no more than 2 mm away from the clival line in the lateral view, when the needle pierces the medial part of the FO toward the medial part of the trigeminal impression in the petrous ridge, and no more than 4 mm in the lateral part. The 40°/45° inferior transfacial–20° oblique radiographic projection visualized 96.2% of the FOs in dry skulls, and the remainder were not visualized in any other projection of the radiograph. Patients with V1 involvement experienced postoperative pain more frequently than did patients with V2 or V3 involvement. Anatomical targeting of V1 in specimens was more efficiently achieved by inserting the needle in the medial third of the FO; for V2 targeting, in the middle of the FO; and for V3 targeting, in the lateral third of the FO.

Conclusions. Knowledge of the extracranial and intracranial anatomical relationships of the FO is essential to understanding and avoiding complications during FO puncture. These data suggest that better radiographic visualization of the FO can improve lesioning accuracy depending on the part of the FO to be punctured. The angles and safety distances obtained may help the neurosurgeon minimize complications during FO puncture and TN lesioning.

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Automated intracranial pressure-controlled cerebrospinal fluid external drainage with LiquoGuard®

Automated intracranial pressure-controlled CSF LiquoGuard

Acta Neurochir (2013) 155:1589–1595

LiquoGuard is a new device for intracranial pressure (ICP)-controlled drainage of cerebrospinal fluid (CSF). This present study evaluates the accuracy of ICP measurement via the LiquoGuard device in comparison with Spiegelberg. Thus, we compared data ascertained from simultaneous measurement of ICP using tip-transducer and tip-sensor devices.

Material and Methods A total of 1,764 monitoring hours in 15 patients (range, 52–219 h) were analysed. All patients received an intraventricular Spiegelberg III probe with the drainage catheter connected to the LiquoGuard system. ICP reading of both devices was performed on an hourly basis. Statistical analysis was done by applying Pearson correlation and Wilcoxon-matched pair test (p<0.05).

Results Mean ICP values were 11±5 mmHg (Spiegelberg) and 10±7 mmHg (LiquoGuard); the values measured with both devices correlated well (p=0.001; Pearson correlation =0.349; n=1,764). In two of the 15 patients with slit ventricles, episodes of significant differences in measured values could be observed. Both patients suffering from slit ventricles failed to produce reliable measurement with the external transducer of the LiquoGuard.

Conclusions LiquoGuard is a valuable new device for ICP-controlled CSF drainage. However, LiquoGuard tends to provide misleading results in slit ventricles. Thus, before these drawbacks are further analysed, the authors recommend additional ICP measurement with internal tip-sensor devices to avoid dangerous erroneous interpretation of ICP data.

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ELTD1, a Potential New Biomarker for Gliomas

ELTD1, a Potential New Biomarker for Gliomas

Neurosurgery 72:77–91, 2013

Glioblastoma multiforme (GBM), a high-grade glioma, is characterized by being diffuse, invasive, and highly angiogenic and has a very poor prognosis. Identification of new biomarkers could help in the further diagnosis of GBM.

OBJECTIVE: To identify ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) as a putative gliomaassociated marker via a bioinformatic method.

METHODS: We used advanced data mining and a novel bioinformatics method to predict ELTD1 as a potential novel biomarker that is associated with gliomas. Validation was done with immunohistochemistry, which was used to detect levels of ELTD1 in human high-grade gliomas and rat F98 glioma tumors. In vivo levels of ELTD1 in rat F98 gliomas were assessed using molecular magnetic resonance imaging.

RESULTS: ELTD1 was found to be significantly higher (P = .03) in high-grade gliomas (50 patients) compared with low-grade gliomas (21 patients) and compared well with traditional immunohistochemistry markers including vascular endothelial growth factor, glucose transporter 1, carbonic anhydrase IX, and hypoxia-inducible factor 1a. ELTD1 gene expression indicates an association with grade, survival across grade, and an increase in the mesenchymal subtype. Significantly high (P , .001) in vivo levels of ELTD1 were additionally found in F98 tumors compared with normal brain tissue.

CONCLUSION: Results of this study strongly suggests that associative analysis was able to accurately identify ELTD1 as a putative glioma-associated biomarker. The detection of ELTD1 was also validated in both rodent and human gliomas and may serve as an additional biomarker for gliomas in preclinical and clinical diagnosis of gliomas.

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Frontal cortico-subcortical functional anatomy

Subcortical surgical anatomy of the lateral frontal region

J Neurosurg 117:1053–1069, 2012

Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon’s awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome.

Methods. Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition.

Results. The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth.

Conclusions. Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

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The intracranial volume pressure response in increased intracranial pressure patients

The intracranial volume pressure response in increased intracranial pressure patients- Part 1

Acta Neurochir (2012) 154:2271–2275

The intracranial pressure (ICP) is usually continuously monitored in the management of patients with increased ICP. The aim of this study was to discover a mathematic equation to express the intracranial pressure– volume (P–V) curve and a single indicator to reflect the status of the curve.

Methods Patients with severe brain damage who had bilateral external ventricular drainage (EVD) from December 2008 to February 2010 were included in this study. The EVD was used as drainage of CSF and ICP monitor. The successive volume pressure response values were obtained by successive drainage of CSF from ICP 20–25 to 10 mmHg. Parabolic, exponential, and linear regression models were designed to have a single parameter as the indicator to determine the P–V curves.

Results The mean of parameter “a” in the exponential equation is 1.473±0.054; in the parabolic equation, it is 0.332±0.061; and in the linear equation, it is 1.717±0.209. All regression equations of P–V curves had statistical significance (p<0.005). Parabolic and exponential equations are closer to the original ICP curve than linear equation (p< 0.005). There is no statistically significant difference between parabolic and exponential regressions.

Conclusions The P–V curve can be expressed with linear, parabolic, and exponential regression models in increased ICP patients. The parabolic and exponential equations are more accurate methods to represent the P–V curve. The single parameter in the three regression equations can be compared in different conditions of one patient in clinical practice.

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Comparison of Indocyanine Green Angiography and Laser Speckle Contrast Imaging for the Assessment of Vasculature Perfusion

Neurosurgery 71:1023–1031, 2012

Assessment of the vasculature is critical for overall success in cranial vascular neurological surgery procedures. Although several methods of monitoring cortical perfusion intraoperatively are available, not all are appropriate or convenient in a surgical environment. Recently, 2 optical methods of care have emerged that are able to obtain high spatial resolution images with easily implemented instrumentation: indocyanine green (ICG) angiography and laser speckle contrast imaging (LSCI).

OBJECTIVE: To evaluate the usefulness of ICG and LSCI in measuring vessel perfusion.

METHODS: An experimental setup was developed that simultaneously collects measurements of ICG fluorescence and LSCI in a rodent model. A 785-nm laser diode was used for both excitation of the ICG dye and the LSCI illumination. A photothrombotic clot model was used to occlude specific vessels within the field of view to enable comparison of the 2 methods for monitoring vessel perfusion.

RESULTS: The induced blood flow change demonstrated that ICG is an excellent method for visualizing the volume and type of vessel at a single point in time; however, it is not always an accurate representation of blood flow. In contrast, LSCI provides a continuous and accurate measurement of blood flow changes without the need of an external contrast agent.

CONCLUSION: These 2 methods should be used together to obtain a complete understanding of tissue perfusion.

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Biomechanical evaluation of the Total Facet Arthroplasty System

Eur Spine J (2012) 21:1660–1673. DOI 10.1007/s00586-012-2253-8

To gain insight into a new technology, a novel facet arthroplasty device (TFAS) was compared to a rigid posterior fixation system (UCR). The axial and bending loads through the implants and at the bone-implant interfaces were evaluated using an ex vivo biomechanical study and matched finite element analysis. Kinematic behaviour has been reported for TFAS, but implant loads have not. Implant loads are important indicators of an implant’s performance and safety. The rigid posterior fixation system is used for comparison due to the extensive information available about these systems.

Methods Unconstrained pure moments were applied to 13 L3–S1 cadaveric spine segments. Specimens were tested intact, following decompression, UCR fixation and TFAS implantation at L4–L5. UCR fixation was via standard pedicle screws and TFAS implantation was via PMMAcemented transpedicular stems. Three-dimensional 10 Nm moments and a 600 N follower load were applied; L4–L5 disc pressures and implant loads were measured using a pressure sensor and strain gauges, respectively. A finite element model was used to calculate TFAS bone-implant interface loads.

Results UCR experienced greater implant loads in extension (p<0.004) and lateral bending (p<0.02). Under flexion, TFAS was subject to greater implant moments (p<0.04). At the bone-implant interface, flexion resulted in the smallest TFAS (average = 0.20 Nm) but greatest UCR (1.18 Nm) moment and axial rotation resulted in the greatest TFAS (3.10 Nm) and smallest UCR (0.40 Nm) moments. Disc pressures were similar to intact for TFAS but not for UCR (p<0.04).

Conclusions These results are most applicable to the immediate post-operative period prior to remodelling of the bone-implant interface since the UCR and TFAS implants are intended for different service lives (UCR—until fusion, TFAS—indefinitely). TFAS reproduced intact-like anterior column load-sharing—as measured by disc pressure. The highest bone-implant moment of 3.1 Nm was measured in TFAS and for the same loading condition the UCR interface moment was considerably lower (0.4 Nm). For other loading conditions, the differences between TFAS and UCR were smaller, with the UCR sometimes having larger values and for others the TFAS was larger. The long-term physiological meaning of these findings is unknown and demonstrates the need for a better understanding of the relationship between spinal arthroplasty devices and the host tissue as development of next generation motionpreserving posterior devices that hope to more accurately replicate the natural functions of the native tissue continues.

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Intracellular Signaling Pathways and Size, Shape, and Rupture History of Human Intracranial Aneurysms

Neurosurgery 70:1565–1573, 2012 DOI: 10.1227/NEU.0b013e31824c057e

Size and morphological features are associated with intracranial aneurysm (IA) rupture. The cellular mechanisms of IA development and rupture are poorly known.
OBJECTIVE: We studied the expression and phosphorylation of different intracellular signaling molecules in the IA wall compared with IA morphological features to understand better the cellular pathways involved in IA development and wall degeneration.
METHODS: Nine ruptured and 17 unruptured human IA samples were collected intraoperatively. The expression levels and phosphorylation state of 3 mitogen-activated protein kinases (c-Jun N-terminal kinase [JNK], p38, extracellular signal-regulated kinase [ERK]), Bcl-2 antagonist of cell death (Bad), mammalian target of rapamycin (mTOR), cyclic AMP response element binding protein (CREB), and Akt were determined by Western blotting. The localization of signaling proteins was determined by immunofluorescence. From 3-dimensional segmentation of computed tomography angiographic data, size and shape indexes were calculated.
RESULTS: We found a 5-fold difference in phospho-Bad levels between ruptured and unruptured IAs. Phospho-mTOR was downregulated 2.5-fold in ruptured IAs. Phosphop54 JNK, phospho-p38, and phospho-Akt levels correlated positively with IA size. Phospho-CREB levels were significantly associated with nonsphericity and ellipticity indexes. Phospho-Akt and phospho-p38 correlated negatively with undulation index.
CONCLUSION: The signaling pathway profile (apoptosis, cell proliferation, stress signaling) differs between ruptured and unruptured IAs and is associated with IA geometry. Our results increase the knowledge of IA development and wall degeneration.

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The intermediate trunk of the middle cerebral artery

J Neurosurg 116:1024–1034, 2012

(http://thejns.org/doi/abs/10.3171/2012.1.JNS111013)

The branching structure of the middle cerebral artery (MCA) remains a debated issue. In this study the authors aimed to describe this branching structure in detail.

Methods. Twenty-seven fresh, human brains (54 hemispheres) obtained from routine autopsies were used. The cerebral arteries were first filled with colored latex and contrast agent, followed by fixation with formaldehyde. All dissections were done under a microscope. During examination, the trunk structures of the MCA and their relations with cortical branches were demonstrated. Lateral radiographs of the same hemispheres were then obtained and comparisons were made. Angles between the MCA trunks were measured on 3D CT cerebral angiography images in 25 patients (50 hemispheres), and their correlations with the angles obtained in the cadaver brains were evaluated.

Results. A new classification was made in relation to the terminology of the intermediate trunk, which is still a subject of debate. The intermediate trunk was present in 61% of cadavers and originated from a superior trunk in 55% and from an inferior trunk in 45%. Cortical branches supplying the motor cortex (precentral, central, and postcentral arteries) significantly originated from the intermediate trunk, and the diameter of the intermediate trunk significantly increased when it originated from the superior trunk. In measurements of the angles between the superior and intermediate trunks, it was found that the intermediate trunk had significant dominance in supplying the motor cortex as the angle increased. The intermediate trunk was classified into 3 types based on the angle values and the distance to the bifurcation point as Group A (pseudotrifurcation type), Group B (proximal type), and Group C (distal type). Group A trunks were seemingly closer to the trifurcation structure that has been reported on in the literature and was seen in 15%. Group B trunks were the most common type (55%), and Group C trunks were characterized as the farthest from the bifurcation point. Group C trunks also had the smallest diameter and fewest cortical branches. Similarities were found between the angles in cadaver specimens and on 3D CT cerebral angiography images. Beyond the separation point of the MCA, trunk structures always included the superior trunk and inferior trunk, and sometimes the intermediate trunk.

Conclusions. Interrelations of these vascular structures and their influences on the cortical branches originating from them are clinically important. The information presented in this study will ensure reliable diagnostic approaches and safer surgical interventions, particularly with MCA selective angiography.

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Analysis of the uncinate processes of the cervical spine

J Neurosurg Spine 16:402–407, 2012. http://thejns.org/doi/abs/10.3171/2011.12.SPINE11541

Although the uncovertebral region is neurosurgically relevant, relatively little is reported in the literature, specifically the neurosurgical literature, regarding its anatomy. Therefore, the present study aimed at further elucidation of this region’s morphological features.

Methods. Morphometry was performed on the uncinate processes of 40 adult human skeletons. Additionally, range of motion testing was performed, with special attention given to the uncinate processes. Finally, these excrescences were classified based on their encroachment on the adjacent intervertebral foramen.

Results. The height of these processes was on average 4.8 mm, and there was an inverse relationship between height of the uncinate process and the size of the intervertebral foramen. Degeneration of the vertebral body (VB) did not correlate with whether the uncinate process effaced the intervertebral foramen. The taller uncinate processes tended to be located below C-3 vertebral levels, and their average anteroposterior length was 8 mm. The average thickness was found to be 4.9 mm for the base and 1.8 mm for the apex. There were no significant differences found between vertebral level and thickness of the uncinate process. Arthritic changes of the cervical VBs did not necessarily deform the uncinate processes. With axial rotation, the intervertebral discs were noted to be driven into the ipsilateral uncinate process. With lateral flexion, the ipsilateral uncinate processes aided the ipsilateral facet joints in maintaining the integrity of the ipsilateral intervertebral foramen.

Conclusions. A good appreciation for the anatomy of the uncinate processes is important to the neurosurgeon who operates on the spine. It is hoped that the data presented herein will decrease complications during surgical approaches to the cervical spine.

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Memory Enhancement and Deep-Brain Stimulation of the Entorhinal Area

N Eng J Med, Vol 366(6), 9 February 2012, p 502–509. DOI: 10.1056/NEJMcibr1113400

The medial temporal structures, including the hippocampus and the entorhinal cortex, are critical for the ability to transform daily experience into lasting memories. We tested the hypothesis that deep-brain stimulation of the hippocampus or entorhinal cortex alters memory performance.

METHODS: We implanted intracranial depth electrodes in seven subjects to identify seizure-onset zones for subsequent epilepsy surgery. The subjects completed a spatial learning task during which they learned destinations within virtual environments. During half the learning trials, focal electrical stimulation was given below the threshold that elicits an afterdischarge (i.e., a neuronal discharge that occurs after termination of the stimulus).

RESULTS: Entorhinal stimulation applied while the subjects learned locations of landmarks enhanced their subsequent memory of these locations: the subjects reached these landmarks more quickly and by shorter routes, as compared with locations learned without stimulation. Entorhinal stimulation also resulted in a resetting of the phase of the theta rhythm, as shown on the hippocampal electroencephalogram. Direct hippocampal stimulation was not effective. In this small series, no adverse events associated with the procedure were observed.

CONCLUSIONS: Stimulation of the entorhinal region enhanced memory of spatial information when applied during learning.

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Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus

Neuroradiology (2012) 54:189–196. DOI 10.1007/s00234-011-0871-1

Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics.

Methods In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N=14) and secondary (N=6) NPH prior and after (91±16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters μ and α, related to the inherent rigidity and topology of the mechanical network of brain tissue.

Results The viscoelastic parameters μ and α were found to be decreased with −25% and −10%, respectively, compared to age-matched controls (P<0.001). Interestingly, α increased after shunt placement (P<0.001) to almost normal values whereas μ remained symptomatically low.

Conclusion The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded.

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The V2 segment of the vertebral artery: anatomical considerations and surgical implications

J Neurosurg Spine 15:610–619, 2011. DOI: 10.3171/2011.7.SPINE1132
Iatrogenic injury of the V2 segment of the vertebral artery (VA) is a rare but serious complication and can be catastrophic. The purpose of this study was to characterize the relationship of the V2 segment of the VA to the surrounding anatomical structures and to highlight the potential site and mechanisms of injury that can occur during common neurosurgical procedures involving the subaxial cervical spine.
Methods. Ten adult cadaveric specimens (20 sides) were included in this study. Quantitative anatomical measurements between selected landmarks and the VA were obtained. In addition, lateral mass screws were placed bilaterally, from C-3 to C-7, reproducing either the Magerl technique or a modified technique. The safety angle, defined as the axial deviation from the screw trajectory needed to injure the VA, and the distance from the entry point to the VA were measured at each level for both techniques.
Results. The VA coursed closer to the midline at C3–4 and C4–5 (mean distance [SD] 14.9 ± 1.1 mm) than at C2–3 or C5–6. Within the intertransverse space it coursed closer to the uncinate processes of the vertebral bodies (1.8 ± 1.1 mm) than to the anterior tubercle of the transverse processes (3.4 ± 1.6 mm). The distance between the VA and the uncinate process was less at C3–6 (1.3 ± 0.7 mm) than at C2–3 (3.3 ± 0.8 mm). The VA coursed on average at a distance of 11.9 ± 1.7 mm from the anterior and 4.2 ± 2.6 mm from the posterior aspect of the intervertebral disc space. Lateral mass screw angles were 25° lateral and 39.1° cranial for the Magerl technique, and 36.6° lateral and 46.1° cranial for the modified technique. The safety angle was greater and screw length longer when using this modified technique.
Conclusions. The relation of the V2 segment of the VA to anterior procedures and lateral mass instrumentation at the subaxial cervical spine was reviewed in this study. A detailed anatomical knowledge of the V2 segment of the VA combined with careful preoperative imaging is mandatory for safe cervical spine surgery.

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The molecular biology and novel treatments of vestibular schwannomas

J Neurosurg 115:906–914, 2011. DOI: 10.3171/2011.6.JNS11131

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin.

Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development.

Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment.

In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1.

A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma.

Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation.

With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

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Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma

Neuro-Oncology DOI:10.1093/neuonc/nor169

Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma.

The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers.

With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver- operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma.

In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas.

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Comparative Morphological Analysis of the Geometry of Ruptured and Unruptured Aneurysms

Neurosurgery 69:349–356, 2011 DOI: 10.1227/NEU.0b013e31821661c3

The risk of aneurysm rupture appears to be related to multiple factors such as topology, morphology, size, perianeurysmal environment, and blood flow hemodynamics.

OBJECTIVE: To evaluate aneurysm morphology and to quantitatively compare the volumetric parameters between ruptured and unruptured aneurysms from our clinical database at the UCLA Medical Center.

METHODS: Novel algorithms that automatically compute aneurysm geometry were tested on the basis of voxel data obtained from angiographic images, and measurements of aneurysm morphology were automatically recorded. We studied a total of 50 aneurysms (25 ruptured and 25 unruptured) with sizes ranging from 3 to 26 mm. To compare the geometric characteristics between ruptured and unruptured groups, we examined measurements, including volume and surface area, and the ratios of these measurements to the minimal bounding sphere around each aneurysm.

RESULTS: More than 65% of ruptured aneurysms had a ratio of aneurysm volume to bounding sphere volume (AVSV) of > 0.5. More than 70% of ruptured aneurysms had a ratio of aneurysm surface to bounding sphere surface (AASA) of < 1. A trend differentiating ruptured and unruptured aneurysms was observed in AVSV (P = .07) and AASA (P = .04). Classification and regression trees analysis showed 68% correct classification with rupture for AVSV and 70% for AASA.

CONCLUSION: By comparing aneurysm geometry with the bounding sphere, we found a trend associating the ratios of aneurysm volume and surface area with rupture. These geometric parameters may be useful for understanding the influence of morphology on the risk of aneurysm rupture.

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Segmental anatomy of cerebellar arteries: a proposed nomenclature

J Neurosurg 115:387–397, 2011.DOI: 10.3171/2011.3.JNS101413

The conceptual division of intracranial arteries into segments provides a better understanding of their courses and a useful working vocabulary. Segmental anatomy of cerebral arteries is commonly cited by a numerical nomenclature, but an analogous nomenclature for cerebellar arteries has not been described. In this report, the microsurgical anatomy of the cerebellar arteries is reviewed, and a numbering system for cerebellar arteries is proposed.

Methods. Cerebellar arteries were designated by the first letter of the artery’s name in lowercase letters, distinguishing them from cerebral arteries with the same first letter of the artery’s name. Segmental anatomy was numbered in ascending order from proximal to distal segments.

Results. The superior cerebellar artery was divided into 4 segments: s1, anterior pontomesencephalic segment; s2, lateral pontomesencephalic segment; s3, cerebellomesencephalic segment; and s4, cortical segment. The anterior inferior cerebellar artery was divided into 4 segments: a1, anterior pontine segment; a2, lateral pontine segment; a3, flocculopeduncular segment; and a4, cortical segment. The posterior inferior cerebellar artery was divided into 5 segments: p1, anterior medullary segment; p2, lateral medullary segment; p3, tonsillomedullary segment; p4, telovelotonsillar segment; and p5, cortical segment.

Conclusions. The proposed nomenclature for segmental anatomy of cerebellar artery complements established nomenclature for segmental anatomy of cerebral arteries. This nomenclature is simple, easy to learn, and practical. The nomenclature localizes distal cerebellar artery aneurysms and also localizes an anastomosis or describes a graft’s connections to donor and recipient arteries. These applications of the proposed nomenclature with cerebellar arteries mimic the applications of the established nomenclature with cerebral arteries.

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Diffusion tensor imaging in the cervical spinal cord

Eur Spine J (2011) 20:422–428. DOI 10.1007/s00586-010-1587-3

There are discrepancy between MR findings and clinical presentations. The compressed cervical cord in patients of the spondylotic myelopathy may be normal on conventional MRI when it is at the earlier stage or even if patients had severe symptoms. Therefore, it is necessary to take a developed MR technique—diffusion tensor imaging (DTI)—to detect the intramedullary lesions.

Prospective MR and DTI were performed in 53 patients with cervical compressive myelopathy and twenty healthy volunteers. DTI was performed along six non-collinear directions with single-shot spin echo echo-planar imaging (EPI) sequence. Intramedullary apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in four segments (C2/3, C3/4, C4/5, C5/6) for volunteers, in lesions (or the compressed cord) and normal cord for patients. DTI original images were processed to produce color DTI maps.

In the volunteers’ group, cervical cord exhibited blue on the color DTI map. FA values between four segments had a significant difference (P<0.01), with the highest FA value (0.85 ±  0.03) at C2/3 level. However, ADC value between them had no significant difference (P> 0.05). For patients, only 24 cases showed hyperintense on T2-weighted image, while 39 cases shown patchy green signal on color DTI maps. ADC and FA values between lesions or the compressed cord and normal spinal cord of patients had a significant difference (both P< 0.01). FA value at C2/3 cord is the highest of other segments and it gradually decreases towards the caudal direction. Using single-shot spin echo EPI sequence and six non-collinear diffusion directions with b  value of 400 s mm-2 ,

DTI can clearly show the intramedullary microstructure and more lesions than conventional MRI.

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